2-Trifluoromethylpyridines and 6-trifluoromethylpyridine-3-carboxylic acid derivatives are intermediates for the preparation of biologically active compounds. For instance, WO 00/39094 A1 discloses trifluoromethylpyridine as herbicides, WO 2006/059103 A2 discloses trifluoromethylpyridines as intermediates in the production of pharmaceutical, chemical and agro-chemical products, WO 2008/013414 A1 discloses trifluoromethylpyridines as vanilloid receptor antagonists and WO 2012/061926 A1 describes trifluoromethylpyridines as calcium channel blockers.
The common route for the preparation of 6-trifluoromethylpyridine-3-carboxylic acid derivatives was first reported by Okada et al., Heterocycles 1997, 46, 129-132, and has only been slightly modified by others. The common synthetic strategies are summarized in Scheme 1:

This route has disadvantages for the large scale production of 6-trifluoromethylpyridine-3-carboxylic acid derivatives, because ethylvinylether is highly flammable and therefore difficult to handle, and because the trifluoroacetylated enolether and the trifluoroacetylated enamine intermediates are unstable and cannot be stored for a longer time. Moreover, most vinyl ethers are mutagenic.
Volochnyuk et al., Synthesis 2003, 10, 1531-1540, discloses a method for the preparation of pyridines substituted in position 4 with a trifluoromethyl residue. The pyridines are part of a bicyclic heterocycle. The method starts with aminopyrazole, which is reacted with trifluoroacetylketones or with the ethyl ester of trifluoroacetylacetic acid. The method is principally not suited to prepare the desired 6-trifluoromethylpyridine-3-carboxylic acid derivatives of the instant invention, since position 6 in Volochnyuk is the endocyclic C atom connecting the pyrazol part with the pyridine part of the bicyclic heterocycle of Volochnuyk. The disclosure does not mention the use of trifluoroacetylacetic acid at all.
WO 2004/078729 A1 discloses the preparation of compound of formula (Xa) from inter alia 4-alkoxy-1,1,1-trifluorobut-3-en-2-ones, which are prepared from vinylethers;
and discloses on page 18 in example P2 the use of 4-ethoxy-1,1,1-trifluorobut-3-en-2-one for the preparation of compound of formula (I-2).

Compound of formula (Xa) and compound of formula (I-2) are intermediates for the preparation of herbicides.
F. Swarts, Bulletin de la Classe des Sciences, Academie Royale de Belgique, 1926, 12, 721-725 discloses the preparation of a certain substrate used in instant invention.
There was a need for an improved procedure for the preparation of 6-trifluoromethylpyridine-3-carboxylic acid derivatives.
This need was met by the method of instant invention as outlined below.
R. W. Leiby, J. Org. Chem. 1985, 50, 2926-2929, discloses the reaction of anthranilates with orthoesters, therefore it was expected that enamines, which are structurally comparable to anthranilates, react with orthoesters as well, and which then would no longer be available for a reaction with trifluoroacetylacetic acid to trifluoromethylpyridine.
Unexpectedly, in a mixture containing orthoesters, enamines and trifluoroacetylacetic acid, the formation of trifluoromethylpyridine was observed.
Compared to prior art, the method of the instant invention offers several advantages: Importantly, no vinyl ethers, trifluoroacetylated enolether intermediates or isolated trifluoroacetylated enamine intermediates are required, e.g. as is used in form of a 4-ethoxy-1,1,1-trifluorobut-3-en-2-one, named 1-ethoxy-3-oxo-4-trifluorobutene, in WO 2004/078729 A1, that is the substance (3) in example P2 of the WO 2004/078729 A1, which is prepared e.g. according to Moriguchi, J. Org. Chem., 1995, 60, 3523-3528 from vinylether, as cited in WO 2004/078729 A1 on page 16 lines 8-9. Moreover, the method of the present invention reduces the number of synthetic steps compared to known procedures, what reduces the overall costs.
In the following text, if not otherwise stated, the following meanings are used:    ambient pressure usually 1 bar, depending on the weather;    alkyl means a linear or branched alkyl, examples of alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl and the like;    cyclic alkyl or cyclo alkyl include cyclo aliphatic, bicyclo aliphatic and tricycle aliphatic residues; examples of “cycloalkyl” include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl and adamantyl;    alkoxy means alkyl-O, i.e. the radical obtained by removal of the oxygen-bound hydrogen from an aliphatic alcohol;    (alkoxy)alkoxy refers to alkoxy groups, in which the alkyl group is substituted with one additional alkoxy group; examples of (alkoxy)alkoxy include methoxymethoxy with formula MeO—CH2—O—, 2-(methoxy)ethoxy with formula MeO—CH2—CH2—O— and 2-(cyclopropylmethoxy)ethoxy with formula (C3H5)CH2—O—CH2—CH2—O—;    Ac acetyl;    tBu tertiary butyl;    cyanuric acid chloride 2,4,6-trichloro-1,3,5-triazine    DBU 1,8-diazabicyclo[5.4.0]undec-7-ene;    DABCO 1,4-diazabicyclo[2.2.2]octane;    DMF N,N-dimethylformamide;    DMA N,N-dimethylacetamide;    DMSO dimethylsulfoxide;    dppf 1,1′-bis(diphenylphosphino)ferrocene    halogen means F, Cl, Br or J, preferably F, Cl or Br;    hemiacetal refers to the adduct of an alcohol, for instance methanol or ethanol, with a ketone or with an aldehyde; a hemiacetal may also result upon the addition of water to an enol ether; for instance, the hemiacetal of methanol with trifluoroacetone is F3C—C(OH)(OCH3)—CH3;    hexanes mixture of isomeric hexanes;    hydrate refers to the adduct of water with a ketone or with an aldehyde, for instance, the hydrate of trifluoroacetone is F3C—C(OH)2—CH3;    LDA Lithium diisopropyl amide    NMP N-methyl-2-pyrrolidone;    sulfamic acid HO—SO2—NH2;    THF tetrahydrofuran;    trifluoroacetone 1,1,1-trifluoropropan-2-one;    xylene 1,2-dimethylbenzene, 1,3-dimethylbenzene, 1,4-dimethylbenzene or a mixture thereof.